CA2796942A1 - Method for diagnosing melanocytic proliferations - Google Patents

Method for diagnosing melanocytic proliferations Download PDF

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Publication number
CA2796942A1
CA2796942A1 CA2796942A CA2796942A CA2796942A1 CA 2796942 A1 CA2796942 A1 CA 2796942A1 CA 2796942 A CA2796942 A CA 2796942A CA 2796942 A CA2796942 A CA 2796942A CA 2796942 A1 CA2796942 A1 CA 2796942A1
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Prior art keywords
staining
sac
diagnosis
nevus
melanoma
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CA2796942A
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CA2796942C (en
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Cynthia Magro
Jonathan Zippin
Lonny R. Levin
Jochen Buck
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Cornell University
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Cornell University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/5743Specifically defined cancers of skin, e.g. melanoma
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/527Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving lyase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5026Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects on cell morphology
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5076Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving cell organelles, e.g. Golgi complex, endoplasmic reticulum
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/20Dermatological disorders
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/56Staging of a disease; Further complications associated with the disease

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
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  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
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  • Biochemistry (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Oncology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Physiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Hospice & Palliative Care (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention provides a method for diagnosing a melanocytic proliferation in a subject comprising staining a sample of lesional melanocytes with an antibody against soluble adenylyl cyclase (sAC) and interpreting the sAC staining pattern, which is associated with a diagnosis of a melanocytic proliferation. The sAC staining pattern, which is complex, is discriminatory and distinctive according to the nature of the melanocytic proliferation. The sAC staining pattern comprises one or more of dot-like Golgi staining, broad granular Golgi staining, diffuse cytoplasmic staining, nucleolar staining, incomplete granular nuclear staining, and pan-nuclear staining. The method of the invention is particularly useful in confirming or disaffirming a diagnosis reached through conventional histologic examination of a sample. Additionally, the invention provides a kit for use in interpreting melanocytic proliferations.

Claims (15)

1. A method for diagnosing a melanocytic proliferation in a subject comprising:
(a) obtaining a sample of lesional melanocytes from a subject, (b) staining the sample with an antibody against soluble adenylyl cyclase (sAC) to establish a sAC staining pattern, and (c) interpreting the sAC staining pattern, wherein the sAC staining pattern is associated with a diagnosis of a melanocytic proliferation in the subject.
2. The method of claim 1, wherein the sAC staining pattern comprises one or more staining patterns selected from the group consisting of:
(a) dot-like Golgi staining, (b) broad granular Golgi staining, (c) diffuse cytoplasmic staining, (d) nucleolar staining, (e) incomplete granular nuclear staining, and (f) pan-nuclear staining.
3. The method of claim 2, wherein the sAC staining pattern is indicative of a diagnosis selected from the group consisting of benign nevus, benign capsular nevus, atypical nevus of special sites, dysplastic nevus, conventional atypical Spitz tumor, superficial atypical Spitz tumor, borderline deep penetrating nevus-like lesion, nevoid borderline tumor, lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, nodular melanoma, and metastatic melanoma.
4. The method of claim 3, wherein the sAC staining pattern comprises:
(a) dot-like Golgi staining in more than 25% of lesional melanocytes and/or (b) pan-nuclear staining in 0-25% of lesional melanocytes, which sAC staining pattern is indicative of a diagnosis of benign nevus, benign capsular nevus, atypical nevus of special sites, or dysplastic nevus.
5. The method of claim 3, wherein the sAC staining pattern comprises:
(a) dot-like Golgi staining in 0-25% of lesional melanocytes and/or (b) pan-nuclear staining in more than 25% of lesional melanocytes, which sAC staining pattern is indicative of a diagnosis of lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, nodular melanoma, or metastatic melanoma.
6. The method of claim 2, wherein the sAC staining pattern is used to distinguish between a benign neoplasm and a malignant neoplasm.
7. The method of claim 2, wherein the sAC staining pattern is used to distinguish between a diagnosis of dysplastic nevus and a diagnosis of superficial spreading melanoma.
8. The method of claim 2, wherein the sAC staining pattern is used to distinguish between a diagnosis of superficial atypical Spitz tumor and a diagnosis of superficial spreading melanoma.
9. The method of claim 2, wherein the sAC staining pattern is used to distinguish between a diagnosis of benign capsular nevus and a diagnosis of metastatic melanoma.
10. The method of any one of claims 1-9, wherein the antibody is a monoclonal antibody.
11. The method of claim 10, wherein the monoclonal antibody is R5, R6.2, R7, R14, R21, R33, R37, R40, R41, R47.1, R52, R53, R54, or R59.
12. The method of any one of claims 1-9, wherein the antibody is a polyclonal antibody.
13. The method of any one of claims 1-12, wherein the subject is a human.
14. The method of any of claims 1-13, wherein the method is used in conjunction with conventional histologic examination of the sample.
15. A kit for diagnosing a melanocytic proliferation in a subject comprising:
(a) an antibody against soluble adenylyl cyclase (sAC) and (b) instructional material for staining a sample of lesional melanocytes from a subject to provide a sAC staining pattern and diagnosing a melanocytic proliferation in the subject by interpreting the sAC staining pattern of the sample.
CA2796942A 2010-04-20 2011-04-06 Method for diagnosing melanocytic proliferations Expired - Fee Related CA2796942C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US32617410P 2010-04-20 2010-04-20
US61/326,174 2010-04-20
PCT/US2011/031466 WO2011133327A1 (en) 2010-04-20 2011-04-06 Method for diagnosing melanocytic proliferations

Publications (2)

Publication Number Publication Date
CA2796942A1 true CA2796942A1 (en) 2011-10-27
CA2796942C CA2796942C (en) 2019-09-24

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Family Applications (1)

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CA2796942A Expired - Fee Related CA2796942C (en) 2010-04-20 2011-04-06 Method for diagnosing melanocytic proliferations

Country Status (6)

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US (1) US8859213B2 (en)
EP (1) EP2561355B1 (en)
BR (1) BR112012026837B1 (en)
CA (1) CA2796942C (en)
IL (1) IL222550A (en)
WO (1) WO2011133327A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011031879A2 (en) * 2009-09-09 2011-03-17 Oregon Health & Science University Automated detection of melanoma
CN104981696B (en) 2012-12-11 2017-11-24 康奈尔大学 Diagnosis and the method for the treatment of prostate cancer

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4208479A (en) * 1977-07-14 1980-06-17 Syva Company Label modified immunoassays
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US5132405A (en) 1987-05-21 1992-07-21 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
WO1988009344A1 (en) 1987-05-21 1988-12-01 Creative Biomolecules, Inc. Targeted multifunctional proteins
WO1989012690A1 (en) 1988-06-13 1989-12-28 American Biogentic Sciences, Inc. Method for the production of monoclonal antibodies utilizing a germfree animal
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US6544768B1 (en) * 1999-05-11 2003-04-08 Cornell Research Foundation, Inc. Mammalian soluble adenylyl cyclase
WO2005070419A1 (en) * 2004-01-21 2005-08-04 Cornell Research Foundation, Inc. Chemical inhibitors of soluble adenylyl cyclase (sac)
EP2518509B1 (en) 2008-03-05 2014-05-14 The Regents of the University of California Molecular prognosis and classification of malignant melanoma based upon markers selected from the list consisting of RGS1, NCOA3, SPP1, PHIP.

Also Published As

Publication number Publication date
CA2796942C (en) 2019-09-24
BR112012026837B1 (en) 2020-04-07
IL222550A0 (en) 2012-12-31
EP2561355B1 (en) 2014-06-18
WO2011133327A1 (en) 2011-10-27
EP2561355A1 (en) 2013-02-27
IL222550A (en) 2016-02-29
US20130065246A1 (en) 2013-03-14
AU2011243118A1 (en) 2012-11-15
BR112012026837A2 (en) 2016-11-29
US8859213B2 (en) 2014-10-14

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